Pregnancy-induced hypertension syndrome arises from placental insufficiency, and is observed in approximately 5 to 7% of pregnant women (Lancet. 2006 Apr. 1; 367(9516): 1066-74, WHO analysis of causes of maternal death: a systematic review (Non-patent Document 1)). Pregnancy-induced hypertension syndrome is a major cause of maternal and infant morbidity and mortality, and the only established therapy is to terminate pregnancy and remove the placenta. Therefore, generating a suitable animal model is extremely significant clinically for understanding the cause of the disease and developing therapeutic agents. Maynard et al. have reported that an increase of soluble FLT1 (sFLT1) and decreases of VEGF and PIGF (placental growth factor, placenta-derived VEGF-like protein) in the mother's blood are observed in women with pregnancy-induced hypertension syndrome (J Clin Invest. 2003 March; 111(5): 649-58, Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. (Non-patent Document 2)). Since sFLT1 is a soluble form of a VEGF receptor, and antagonizes the functions of VEGF and PIGF, it is considered that sFLT1 causes functional disorders of the vascular endothelium and pregnancy-induced hypertension syndrome due to the impairment of angiogenic signaling (N Engl J. Med. 2004 Feb. 12; 350(7): 672-83. Circulating angiogenic factors and the risk of preeclampsia. (Non-patent Document 3)). This is also supported by the fact that systemic administration of an adenovirus vector (AdV-) that expresses sFLT1 to pregnant rats showed hypertension, proteinuria, and glomerulosclerosis which are classical pathological changes in pregnancy-induced hypertension syndrome (J Clin Invest. 2003 March; 111(5): 649-58, Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. Long-term maternal cardiovascular function in a mouse model of sFlt-1-induced preeclampsia. (Non-patent Document 2)). However, while sFLT1 is expressed in pregnancy-induced hypertension syndrome until delivery, sFLT1 expression in a model animal was transient. Furthermore, in conventional model animals, since sFLT1 is produced in the mother's body (mainly liver) but not in the placenta which is the causative organ, the pathological condition does not improve upon delivery. That is, the conventional model animals are defective as models for pregnancy-induced hypertension syndrome which shows improvement of pathological conditions upon delivery.
Meanwhile, it has been proven that when blastocyst-stage embryos are infected with a lentiviral vector, genes can be introduced into the placenta alone without being transfected into the mother's body and the unborn baby (Non-patent Documents 4 and 5).